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THE NATIONAL DRUG ABUSE TREATMENT CLINICAL TRIALS NETWORK RELEASE DATE: July 07, 2004 RFA Number: RFA-DA-05-001 EXPIRATION DATE: October 15, 2004 Department of Health and Human Services (DHHS) PARTICIPATING ORGANIZATION: National Institutes of Health (NIH) (http://www.nih.gov) COMPONENT OF PARTICIPATING ORGANIZATION: National Institute on Drug Abuse (NIDA) (http://www.nida.nih.gov) CATALOG OF FEDERAL DOMESTIC ASSISTANCE NUMBER: 93.279 LETTER OF INTENT RECEIPT DATE: September 14, 2004 APPLICATION RECEIPT DATE: October 14, 2004 THIS REQUEST FOR APPLICATIONS (RFA) CONTAINS THE FOLLOWING INFORMATION: o Purpose of this RFA o Research Objectives o Mechanism(s) of Support o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Special Requirements o Where to Send Inquiries o Letter of Intent o Submitting an Application o Supplementary Instructions o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE OF THIS RFA The National Institute on Drug Abuse (NIDA) invites cooperative agreement applications from established clinical investigators to participate in the National Drug Abuse Treatment Clinical Trials Network (CTN). Applications from geographic areas not currently well represented in the CTN are particularly encouraged. This Request for Applications (RFA) is the fourth solicitation for participation in the CTN. It is intended for both new applications and competing continuations. As a nation-wide partnership among drug abuse treatment providers, researchers, and NIDA staff, the mission of the CTN is to conduct studies of behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions in rigorous, multi-site clinical trials to determine the effectiveness of these interventions across a broad range of community- based treatment settings and diverse patient populations. The CTN disseminates and promotes the adoption of proven treatments to physicians, providers, their patients, accrediting bodies, educational institutions, policy makers and funders to improve the quality of drug abuse treatment throughout the country, using science as the vehicle. CTN clinical trials are carried out in community-based treatment settings. Each awardee functions as a CTN Research Node, consisting of a Regional Research and Training Center (RRTC) that is linked in partnership with community-based treatment programs (CTPs). The CTN consists of multiple Nodes, and each Node works in concert with other Nodes and NIDA to conduct multi-site clinical trials research. Awardees deliver and test an array of both behavioral and pharmacological treatments and determine conditions under which novel and efficacious treatments are successfully adopted. Studies span multiple sites engaging diverse patient populations in dispersed geographical regions. As a cooperative agreement, there is substantial NIDA involvement in the management and administration of the CTN. Current CTN Nodes are located in California, Colorado, Connecticut, Florida, Maryland, Massachusetts, Michigan, New Mexico, New York, North Carolina, Ohio, Oregon, Pennsylvania, South Carolina, and Washington. NIDA recognizes a benefit in a greater geographic distribution of CTN sites as well as a desire to encompass more subpopulations of minority groups and to broaden the range of treatment providers who work under varying systems of reimbursement and organization of care. By expanding in these areas, greater variety in the types of studies conducted and greater confidence in the generalizability of those studies will be assured. Therefore, as noted, one purpose of this Request for Applications (RFA) is to expand the geographic distribution of CTN sites, and applications are encouraged from investigators in those geographic areas without CTN Nodes and where the CTN is not well represented. Another purpose is to enable eleven existing Nodes to re-compete to continue participation within the CTN for another five years. RESEARCH OBJECTIVES Background The development of the CTN was based, in part, upon a recommendation from the National Advisory Council on Drug Abuse and conclusions of the Physicians Leadership on National Drug Policy. The Institute of Medicine/National Academy of Sciences report "Bridging the Gap Between Practice and Research: Forging Partnerships with Community-Based Drug and Alcohol Treatment" also recommended a national network for drug abuse treatment trials. Following the first NIDA CTN solicitation in 1999, six CTN awards were made to awardees in California, Connecticut, New York, Oregon, Maryland, and Pennsylvania. After a solicitation in 2000, awards were subsequently made to five additional sites in Colorado, Florida, Michigan, Ohio, and South Carolina. In 2001 three additional sites were awarded in New York (Long Island), North Carolina and Washington. In 2002 there were three additional sites added in California, Massachusetts, and New Mexico. These sites represent a variety of treatment traditions that include pharmacological as well as behavioral and other psychosocial interventions. Furthermore, NIDA ensured a wide variety of patient populations in the selection of CTN recipients. Women, minority groups, and adolescents are well represented. The CTN is now established and is making progress in achieving its goals of (1) providing a clinical trials research infrastructure to test the effectiveness and usefulness of new and improved treatments in community- based treatment settings with diverse patient populations, (2) serving as a mechanism for the study of dissemination of new and improved interventions into community-based drug treatment settings and (3) providing unique opportunities to train clinical researchers. The infrastructure of the CTN is available for non-network researchers to use a study platform. A number of functional committees to provide governance to the CTN are established, protocols for the study of both pharmacological and behavioral interventions are currently underway, data management and safety monitoring procedures are in place, and new studies are being planned and approved. Details on the status of the CTN initiative may be found on the NIDA web site at: http://www.nida.nih.gov/CTN/Index.htm. Strong partnerships and bi-directional collaboration between researchers and practitioners are an essential and defining characteristic of the CTN. Although treatments for drug abuse exist and considerable research has been directed toward the improvement of treatment alternatives, most addiction treatment research prior to the CTN was conducted primarily in specialized research settings. Through the researcher-practitioner partnership that characterizes the CTN, the CTN accelerates the use of research outcomes, the pace of research, and its application to community treatment settings by conducting large scale multi-site clinical treatment studies in community based treatment programs (CTPs). Knowledge gained through the CTN is also expected to further the dissemination and the adoption of research-based treatments. That is, CTN research will not only help determine which treatments should be implemented, it will also inform the process of implementation and dissemination to ensure the acceptability and sustainability of new approaches CTN DEFINITIONS, ORGANIZATION, AND FUNCTIONS Clinical Trials Network (CTN). A collaborative group of geographically diverse regional research Nodes working collaboratively with NIDA to conduct multi-site and cross-regional (nationwide) clinical trials research on promising behavioral, pharmacological, or integrated drug abuse treatments. Node. A Node is the functional unit within the CTN. The Node consists of the Regional Research and Training Center (RRTC) and its affiliated Community Treatment Programs (CTPs). The RRTC coordinates and arranges a research partnership between the RRTC and CTPs. The CTN is comprised of multiple Nodes. Activities that occur primarily within a single Node (e.g., hiring of staff, RRTC-CTP activities) are called "Intra-Node" activities, as opposed to CTN-wide or "Inter-Node" activities such as implementation of protocols across one or more Nodes, development of CTN-wide policies, etc. A "Lead Node" is a Node that has primary responsibility for leading a research project. Regional Research and Training Center (RRTC). The RRTC is the recipient of the cooperative agreement award. It is one of the two components of a Node. It typically resides in the Principal Investigator’s research institute or organization. The RRTC provides scientific leadership and design of clinical trials. The RRTC has primary responsibility for 1) establishing the infrastructure, 2) generating a research agenda in collaboration with the CTPs, 3) providing administration and operations support, 4) building partnerships with the CTPs, and, 5) collaborating with NIDA and other Nodes to develop, implement, and disseminate findings from CTN research projects, and 6) working with the CTN Clinical Coordinating Center and Data and Biostatistics Center. Infrastructure. Infrastructure refers to the capacity of the RRTC and CTPs to 1) arrange and manage collaborative activities of at least five CTPs with the RRTC, 2) maintain scientific and technical personnel for protocol development and implementation, 3) coordinate intra-Node activities, and 4) provide resources for intra-Node activities. It also refers to the physical resources (buildings, clinics, etc.) available. Research Agenda. In partnership with its affiliated CTPs, the RRTC develops and submits research concepts and protocols to the CTN Steering Committee for review and approval. For each approved concept, a protocol specific project team is established to develop and implement the research project across the CTN. It is expected that there will be a Lead Investigator (LI) from the Node where the research concept and protocol originated. NIDA scientific and technical personnel may be designated as collaborators on the project team. The LI assumes the leadership role for all aspects of that specific protocol and serves as the primary liaison to CTN-wide coordination/support centers as needed. The project team for each CTN research project includes personnel and experts across the network from all disciplines required for the development and implementation of the project. Training Agenda: In partnership with the training support for clinical researchers the CCTN strongly encourages the RRTC to apply for training grants to support physicians, clinical psychologists, post-doctoral candidates, and junior faculty. The CTN provides many opportunities for these researchers to gain valuable experience in designing and managing multi-site clinical trials. Administrative and Operations Support. The RRTC ensures appropriate administrative and operational support for Node activities. The support must ensure adherence to the Terms and Conditions of the Award and the policies and procedures of the CTN Steering Committee to: 1) design and develop CTN research projects; 2) formulate and conduct project specific training; 3) develop patient safety and other regulatory documents to obtain approvals needed to implement studies within the Node; and, 4) ensure the quality of research within the Node through on-site monitoring at participating clinical sites. Partnership with and Responsibility toward Affiliated CTPs. The RRTC functions as a partner with its associated CTPs. It provides CTPs with 1) support for the CTP Director representing the Node on the Steering Committee, 2) scientific guidance and mentoring as the RRTC develops research concepts for the CTN 3) support for the CTP Director to participate in Special Interest Groups, Subcommittee activities and protocol development teams 4) support for CTP participation in CTN Blending Meetings. Community Treatment Programs (CTPs). Drug abuse treatment programs in the community setting (typically non-university-based) that have a history of providing quality treatment to large and diverse patient populations, including women, members of minority groups, and adolescents, and have the capability for and interest in participating in controlled clinical trials. Working as an equal partner with its RRTC, each CTP must: o Agree to participate in controlled clinical trials, including randomization methods for assignment of patients to experimental or control groups or randomization of therapists to different conditions; o Screen and recruit adequate numbers of patients required to meet the expectation of specific protocols. This frequently requires recruiting one patient per week. o Agree to provide routine clinical care to patients participating in protocols; o Agree to provide experimental/standard care in accord with approved research protocols; o Provide HIV risk reduction counseling and access to HIV testing; o Provide HCV education and referral for testing and treatment; o Maintain patient records and other source documents required for each protocol; o Collect clinical and laboratory data, including biological specimens when indicated; o Cooperate with quality assurance activities of the CTN and adhere to guidelines set by the RRTC, the Steering Committee, and NIDA; o Cooperate with NIDA’s Clinical Coordinating Center and Data and Statistics Center; o Participate in the development of research concepts and protocols for trials to be conducted in the CTN; o Agree not to report data prior to collaborative reporting; o Agree to periodic on-site audits by representatives of its RRTC, NIDA, or a NIDA designee to ensure appropriate use of investigational drugs; compliance with regulations for IRB approval and informed consent (compliance with 45 CFR 46); compliance with protocol specifications; quality assurance and accuracy of data recording; and completeness of reporting of adverse drug reactions. Principal Investigator. The senior scientist named in the grant by the applicant institution to lead and manage the activities within the Node. CTP Director. The individual designated by the participating community treatment program to represent the CTP on the Node. This individual is also responsible for the CTP’s obligations to the Lead Investigator during the course of a protocol. CTN Steering Committee. The Steering Committee constitutes the primary governing body of the Network. The committee membership consists of the Principal Investigator and one CTP Director from each Node, two NIDA representatives (one of which is the NIDA Director of the Center for Clinical Trials Network), one representative from the CTN Clinical Coordinating Center and one representative from the CTN Data and Statistics Center. This group reviews and approves the research agenda, formulates and monitors policies and procedures guiding the research activities, and oversees communications within the CTN, as well as with the greater scientific community and the public. All major network decisions are determined by majority vote of the Steering Committee. All participating RRTCs and CTPs must agree to abide by the study designs and policies approved by the Steering Committee. It is important to note that research to be undertaken within the CTN is not limited to research concepts contained within awardees’ applications, but are and will be determined by the Steering Committee based on input from the Nodes and subject to the approval of NIDA. Future research must be within and consistent with the scientific objectives of the RFA. The Steering Committee uses established subcommittees and workgroups to assist it in carrying out its functions. The Steering Committee meets no more than four times per year. Applicants should include costs for travel to these Steering Committee meetings and subcommittee/workgroup meetings in their applications and should assure that adequate provisions are made to allow the Principal Investigator, Node personnel and CTP representatives to participate fully in activities of the Steering Committee and its subcommittees and workgroups. http://www.nida.nih.gov/CTN/Index.htm. NIDA Protocol Review Board. An independent expert board authorized by the Director of NIDA to advise the Director CCTN on scientific and regulatory issues. Data and Safety Monitoring Board (DSMB). The DSMB is an independent expert board, appointed by and reporting to the Director of CCTN that oversees and monitors the conduct of the clinical trials to ensure the safety of participants and the validity and integrity of data for each study. The DSMB also makes an independent assessment of the interventions under study and whether or not any trial undertaken in the CTN will continue. One or more NIDA staff serves as non-voting members on the DSMB. Data and Statistics Center (DSC). A contract awarded by NIDA to provide clinical data information systems as required to implement standards established by NIDA and the CTN Steering Committee. Such standards guide development and implementation of the protocol-specific electronic case report form (eCRF) applications that each Node must implement at participating CTP sites. The DSC reports directly to NIDA, although it functions as a resource to the CTN Steering Committee in all matters related to data management--from study design, data acquisition and analyses to report of study findings and conclusions. 1) Provide logistical support for specific trials, e.g. hire research staff, provide computer hardware and software to participating CTPs if needed, and provide Internet access to participating CTPs if needed. 2) Assist the Lead Investigator in protocol development with respect to data management, design and analysis, and interim analysis plan (if applicable). 3) Manage all aspects of data collection. 4) Analyze data to test primary and secondary study hypotheses. 5) Monitor trial progress. 6) Conduct data quality assurance monitoring. 7) Produce reports for the Data and Safety Monitoring Board (DSMB) 8) Provide data/facts that will assist NIDA staff with producing Node performance reports based on CTN’s performance criteria. Clinical Coordinating Center (CCC): NIDA provides via a contract certain resources and common services for CTN clinical trials, including support for administrative requirements and oversight functions mandated by NIH. Specifically: 1) Regulatory affairs and Investigational New Drug (IND) filing; 2) Monitoring for clinical study sites; 3) Administrative support for protocol development; 4) Project management; 5) Training in Good Clinical Practice (GCP) etc.; 6) Central pharmacy services for medication packaging and shipping; 7) Clinical laboratory support. 8) Coordinate activities (face-to-face meetings and/or conference calls) for specific protocols (not core CTN meetings). 9) Coordinate the distribution of trial supplies, e.g. medication, forms, manuals. 10) Coordinate the distribution of materials with laboratories involved in CTN’s clinical trials. 11) Assist the Lead Investigator in protocol development with respect to regulatory, QA and training plans. 12) Provide training of general clinical research conduct (GRP) and CTN protocol common assessment batteries (CAB). 13) Monitor GCP compliance according to the Quality Assurance Plan defined by each Lead Investigator of the protocol. 14) Monitor regulatory compliance. 15) Provide data/facts that will assist NIDA staff with producing Node performance reports based on CTN’s performance criteria. Logistic Support Center (LSC). A contract awarded by NIDA to support many of the administrative and logistic functions of the CTN including: 1) Coordinating logistic and operational support for a variety of CTN meetings with up to 250 attendees; 2) Handling all logistics and costs with coordinating over 400 conference calls on an as needed basis per year; 3) Support for consultants providing NIDA and the CTN grantees with expert advice on a variety of topics regarding the Network; 4) Preparing publicity, meeting, and protocol related materials as required; 5) Providing scientific writers/editors to prepare reports, take minutes of meetings and conference calls, edit documents; 6) Reproducing and distributing research materials, protocol related documents, and educational materials; 7) Creating and maintaining administrative records to support the CTN activities; 8) Providing translation services for CTN materials in languages other than English; 9) Maintaining a CTN web site; and 10) Miscellaneous support services. NOTE: Funds to support Node personnel travel to meetings will not be disbursed by the LSC. Applicants should make adequate provision for these funds in the budgets submitted under the present RFA. See the Subsection "Budget" in the "APPLICATION PACKAGE" section below for more guidance on this issue. Center for the Clinical Trials Network (CCTN). The organization within NIDA responsible for the scientific, administrative, and operational management of the CTN research program funded by NIDA. OBJECTIVES AND SCOPE The overall goal of the National Drug Abuse Treatment Clinical Trials Network is to improve the quality of drug abuse and addiction treatment throughout the Nation using science as the vehicle. Specific objectives include: o A standard frame of reference in research on drug abuse and development of comprehensive drug abuse treatment programs that integrates co-morbid medical/mental health conditions (e.g., mental disorders, HIV, Hepatitis B & C, tuberculosis, sexually transmitted diseases (STDs) and other blood-borne infections. o Supporting rigorous, multi-site clinical trials of efficacious behavioral, pharmacological, and combined behavioral and pharmacological treatment interventions in community-based treatment programs to determine effectiveness across a broad range of treatment settings and patient populations. o Encouraging research on effective strategies for transporting science-based treatment interventions into clinical practice. o Furthering the development of effective treatments by integrating behavioral and pharmacological interventions. o Ensuring that treatment research in drug abuse and addiction is extended to the wider community, such as minorities, women, children, adolescents, and underserved populations. o Ensuring that treatment research in drug abuse and addiction addresses the needs of special populations within the wider community, including court- involved patients and patients with co-morbid psychiatric or medical conditions. o Fostering the collaboration between community practitioners and treatment researchers by providing opportunities for bi-directional education, exchange of ideas, information, and values. o Investigating the impact of community-based treatment research on community treatment practices. o Exploring the effectiveness of behavioral, pharmacological, and integrated behavioral and pharmacological treatment interventions to reduce the transmission of HIV and other disease (such as hepatitis B and C or sexually transmitted infections) and to enhance adherence to treatment for HIV and other disease among drug users. Additionally, small efficacy trials of promising, theoretically grounded behavioral interventions may be conducted. This RFA also seeks a broad range of research on disease prevention for drug users in treatment including, but not limited to, the following topics. o The effectiveness of behavioral and/or pharmacological drug treatment modalities in reducing drug-related transmission risks for HIV and other disease; o The effectiveness of drug use relapse prevention programs and other enhanced engagement-in-drug-treatment interventions in reducing drug-related transmission risks for HIV and other disease; o The effectiveness of culturally appropriate HIV testing and counseling interventions in reducing drug- and sex-related transmission risks among HIV- positive and HIV-negative drug users in drug treatment settings; o The effectiveness of cognitive-behavioral-affective skills building interventions in reducing drug-related transmission risks for HIV and sex- related transmission risks for HIV and other STIs, specifically tailored for heterosexual adults or men who have sex with men; o The effectiveness of developmentally appropriate cognitive-behavioral- affective skills building interventions in reducing drug- and sex-related disease transmission risks among adolescent drug users in treatment; o The effectiveness of peer- or family-based interventions in reducing drug abuse and drug-related transmission risks among adolescents in drug treatment settings; o The effectiveness of psychiatric treatment (e.g., for depression, anxiety, PTSD, ADHD, conduct problems) in reducing drug- and sex-related transmission risks among adolescent or adult substance abusers in drug treatment settings; o The effectiveness of on-site, antiretroviral therapy adherence/compliance counseling for HIV- or HCV-infected drug users in drug treatment; o The effectiveness of providing comprehensive medical services, or linkage to primary care, for HIV-, HCV- or STI-infected drug users in drug treatment. Characteristics of the CTN The CTN provides the Nation with a stable and broadly representative platform for drug abuse treatment research through regional Nodes distributed throughout the country. Each Node encompasses a substantial geographical area and a variety of treatment settings, patient populations, and drug abuse problems. The RRTC of each Node must have demonstrated expertise in conducting drug abuse treatment research, clinical trials and clinical training. Through its associated CTPs, each Node must demonstrate the capacity to recruit and treat a broad range of patients, including adolescents, women, patients with co-occurring mental disorders, those at high risk for HIV infection, members of racial/ethnic groups, and those abusing or addicted to various drugs of abuse. All Nodes must demonstrate the capacity to deliver and test a variety of both pharmacological and behavioral therapies. The term "behavioral therapy" is used here in the broadest sense and is meant to include, for example, counseling, various aspects of therapeutic community approaches, cognitive behavioral therapy, operant behavioral therapy, and family therapy. For the CTN to be maximally effective, the CTPs must be partners in the research enterprise by participating in research decisions, including selection of research concepts to be implemented and decisions concerning protocol design. The CTN has completed several protocols, several are actively enrolling participants, and more are preparing to initiate enrollment. See listing on the web at http://www.nida.nih.gov/CTN/research.html. As the CTN continues to develop, it is anticipated that CTN will be used as a platform so that other topics could be studied such as: o Techniques for transporting new behavioral therapies into community-based treatment groups. For example, the effectiveness of various approaches to therapist training could be compared within the clinical trial context. In this fashion, information can be gained not only about whether a therapy performs better than standard care, but also about how a therapy may be transported. o Optimizing access to and effectiveness of currently marketed pharmacotherapies for treatment of drug abuse and addiction. Examples are studies to determine the optimal approach for integrating medications with behavioral therapies at optimal levels and doses, such as, naltrexone with cognitive behavioral therapy or Buprenorphine with drug addiction counseling. o Behavioral interventions aimed at improving compliance with medication regimens in patients with co-morbid addictive and mental or physical disorders. For example, studies could be done to determine the best behavioral interventions to ensure antiviral medication compliance in drug addicted individuals with AIDS, or to investigate the effectiveness of a new behavioral intervention for patients with bipolar disorder. o Effective therapies for treating marijuana abuse -- particularly in adolescent populations. o Models for integrating new behavioral interventions into existing clinical practices. In the area of HIV/AIDS research, examples are: o Effective approaches to outreach and risk reduction counseling. Drug addiction and the spread of HIV/AIDS are intertwined epidemics, and the CTN will provide a vehicle to help facilitate reduction in risk behaviors given that CTPs participating in the CTN must provide HIV risk reduction counseling and offer HIV testing. o Efficacy of drug abuse treatment on AIDS related outcomes, such as rate of progression to AIDS. Studies could examine the effects of: 1) the early treatment of HIV, Hepatitis B and C and Sexually Transmitted Diseases, or 2) the prevention and early treatment of co-morbid medical and mental health conditions associated with HIV/AIDS infection. Such studies may incorporate the most current methodological advances for assessing a) biological and mental health risks and HIV status, and b) adherence and compliance to antiretroviral and other medical/mental health therapies. The CTN, with its core of CTPs engaging diverse populations, is also designed to provide a platform for health service research and a much needed vehicle to recruit study subjects for such related topics as the genetic vulnerability to addiction, which would be funded under separate research grants. In the area of genetics studies, examples are: o Studies that better describe, disseminate, and predict the complex nature and course of drug abuse and addiction to offer more precise phenotypic indices for testing of hypothesized underlying genetic risk factors associated with drug abuse. o Pharmacogenetics into ongoing medications trials for response to treatment and/or therapeutic outcome. Examples could include accurate and comprehensive descriptions of phenotypes and associations with genotype to disease (phenotype-to-genotype approach), or selection of appropriate candidate gene variants to examine for association to a given drug response or outcome (genotype-to-phenotype approach) In the area of health service research, an example is: o Studies to describe factors impacting transmission of knowledge, change of treatment organizations, and adaptation of new treatments and their adoption into widespread clinical practice. NIDA encourages researchers to study such treatment issues at the organizational/program levels under separate research project grants. Although not all Nodes would be expected to have the capacity to conduct studies in HIV/AIDS, genetics and health services, all Nodes will be expected to collaborate in research focusing on such issues and to aid in recruitment of appropriate subjects. Please reference the CTN policy on using the CTN as a research platform. http://www.nida.nih.gov/CTN/policies.html. Nodes with expertise in these special areas will be given priority when making funding decisions. MECHANISM OF SUPPORT This RFA will use NIH U10 award mechanism(s). As an applicant you will be solely responsible for planning, directing, and executing the proposed project. This RFA is a one-time solicitation. The anticipated award date is August 31, 2005. The NIH (U10) is a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Principal Investigator retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the section "Cooperative Agreement Terms and Conditions of Award" FUNDS AVAILABLE It is expected that each Node will have an operating budget of up to $2.2 million per year, comprised of grant awards of $1.25 million to pay for core support with additional funds available for implementation of protocols. There are also funds to support a separate contract which covers data management, data analysis, and portions of quality assurance monitoring, training and regulatory affairs. NIDA expects to make up to eleven awards under this RFA for project periods of up to 5 years of support. It is anticipated that there will be subsequent RFAs to sustain or expand the CTN. It is projected that competing continuation applications will be invited upon expiration of the initial funding period of awards made under this and previous RFAs, subject to availability of funds. For new applicants, in general, no more than $700,000 in direct costs should be allocated to support first year operations. Therefore, the budgets for ensuing years (year two through year five) should be increased to reflect anticipated costs associated with maintaining the Node infrastructure and performing research projects. Because the role and function of a CTN Research Node is well established, it is expected that the size of individual awards for core support will be similar. Budget requests should be carefully justified and commensurate with the complexity of the project. Although this program is provided for in the financial plans of NIDA, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. ELIGIBLE INSTITUTIONS You may submit (an) application(s) if your institution has any of the following characteristics: o For-profit or non-profit organizations o Public or private institutions, such as universities, colleges, hospitals, and laboratories o Units of State and local governments o Eligible agencies of the Federal government o Domestic institutions/organizations o Foreign institutions are not eligible to apply o Faith-based or community-based organizations INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. The Principal Investigators must commit to and be actively involved in the research and governance of the CTN at a minimum of 50 percent effort and document a substantial history of leadership in clinical trials research and an extensive research publication record. SPECIAL REQUIREMENTS To promote the development of a collaborative program among award recipients, a number of issues need to be addressed in applications as discussed under Application Procedures, below. Applicants should document their ability to recruit a sufficient number of participants, and should demonstrate their ability and willingness to work cooperatively with NIDA, other awardees, and CTPs, and to follow common protocols. The Principal Investigator must commit at least 50% effort to this project. The following terms and conditions will be incorporated into the award statement and are provided to the Principal Investigator(s) as well as the institutional official at the time of award. Cooperative Agreement Terms and Conditions of Award These special Terms of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92, and other HHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is a cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism) in which a substantial NIH scientific and/or programmatic involvement with the Awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or coordinate the recipient’s activity by involvement and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the Awardee(s) for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the Awardees and NIDA and its contractors. This cooperative agreement funding mechanism will require collaboration between the Director of NIDA’s Center for Clinical Trials Network (CCTN) and the Principal Investigators of the CTN Nodes. The NIDA CCTN will assist in coordinating activities of the CTN as defined below and will facilitate the exchange of information. 1. Awardee Rights and Responsibilities Awardees will have primary responsibility for defining the details for the project within the guidelines described in the Request for Applications and for performing the scientific activity, and agree to accept close coordination, cooperation, and participation of NIDA staff in those aspects of scientific and technical management of the project described in these terms and conditions. The awardee further agrees to accept close coordination and to cooperate fully with NIDA designated coordinating centers that will be responsible implementing approved protocols. Specifically, awardees have primary responsibilities as described below. a. Steering Committee: Awardees participate in The National Drug Abuse Treatment Clinical Trials Network (CTN) Steering Committee that serves as the governing body of the CTN. The voting membership of the Steering Committee consists of the Principal Investigator and a CTP Director representative of each RRTC, and two representatives from NIDA, one of which is the NIDA CCTN Director. There are also two representatives from the Clinical Coordinating Center and the Data and Statistics Center. The Steering Committee reviews and approves the research agenda, formulates and monitors policies and procedures guiding the research activities, and oversees communications within the CTN as well as with the greater scientific community and the public. All major decisions are determined by majority vote of the Steering Committee. All participating RRTCs must agree to abide by the study designs and policies approved by the Steering Committee. Research undertaken within the CTN is determined by the Steering Committee based on input from the Nodes and subject to the approval of the Protocol Review Board and NIDA. Future research must be within and consistent with the scientific objectives of the RFA. The Steering Committee policies and standard operating procedures govern all aspects of the CTN including, but not limited to, protocol design and development, protocol review and approval, study operations and standards, data acquisition and management, and data analysis and publication. The Steering Committee has established CTN performance goals and monitors progress throughout the life of the CTN and its research projects. Standard operating procedures and policies governing the CTN are available at http://www.nida.nih.gov/CTN/policies.html. b. Policies/Operating Procedures The Steering Committee Chair will be responsible for ensuring that there are well documented policies and operating procedures guiding all aspects of CTN activities (e.g. protocol development, review, project initiation, conduct, and closure, data collection and management, publication, etc.) and bylaws delineating the requirements and expectations of collaborating institutions, membership criteria, and standards of performance, and procedures for removing institutions due to poor performance. 2. Responsibilities of the CTN Regional Research and Training Center (RRTC): Generally, Awardees under this agreement have the following rights and responsibilities as a National Drug Abuse Treatment Clinical Trials Network (CTN) RRTC: o The RRTC provides a core of administrative and study operations services, as well as scientific leadership and management of clinical trials. The RRTC, acting as the local operating center for a Node, has primary responsibility for 1) establishing an infrastructure for core functions, 2) generating a research agenda, 3) providing the Node with administration and operations support, and 4) building partnerships with the CTPs. o Infrastructure for core functions – This includes but is not limited to 1) arranging and managing the participation of at least five CTPs in the first year, with possibility for expansion in subsequent years, 2) maintaining scientific and technical personnel for protocol development and implementation, 3) coordinating intra-Node activities, and 4) providing resources for intra-Node activities, 5) collaborating with NIDA and other Nodes to develop, implement, and disseminate findings from CTN research projects 6)working with the CTN Clinical Coordinating Center and Data and Statistics Center. o Research Agenda/implementation - In partnership with its affiliated CTPs, the RRTC develops and submits research concepts and protocols to the CTN Steering Committee for review and approval. For each approved concept, a protocol specific project team will be established to develop and implement the research project. It is expected that a Lead Investigator will come from the Node where the research concept and protocol originate. NIDA Staff may be designated as scientific and programmatic collaborators on the project team. The Lead Investigator will assume the leadership role for all aspects of that specific protocol and serve as the primary liaison to CTN-wide coordination/support centers as needed. a. Protocol Development: The Principal Investigator of a RRTC in collaboration with local CTPs, Co- PIs, and other Network colleagues shall initiate the development of a clinical trial concept and once that concept is approved by the Steering Committee and NIDA, the Lead Investigator from that Node shall expeditiously draft a research protocol according to Steering Committee guidelines for protocol content and format. The Steering Committee will review and approve RRTC initiated protocols. Such review will include provisions for NIDA scientific review and comment, including review by an independent CTN Protocol Review Board. The RRTC will be responsible for providing ancillary information about the protocol to permit review of the proposed project’s scientific rationale, feasibility, costs, and compatibility with NIDA research priorities and existing clinical research programs. The Principal Investigators of RRTCs agree to cooperate with NIDA’s contracted Data and Statistical Center with regard to CTN-wide standards for collection and analysis of data generated under the CTN, and enabling the Data and Statistics Center to provide timely, accurate, and complete data for purposes of monitoring the safety and progress of research projects conducted within the CTN, as well as final study data according to schedules developed and approved by the Steering Committee for individual research projects conducted through the CTN. b. Data Rights: The NIH expects investigators supported by NIH funding to make their research data available to the scientific community for subsequent analysis based on a data sharing plan approved as part of the award; see the NIH data sharing policy website at http://grants.nih.gov/grants/policy/data_sharing The CTN is intended as a national resource for the advancement of treatment for addicted individuals and other affected persons. The Awardee of this agreement acknowledges that NIH has access to any and all data generated under this cooperative agreement and the Awardee agrees to provide royalty-free, nonexclusive, and irrevocable license for the government to reproduce, publish, or otherwise use the material and data derived from research conducted under this cooperative agreement. Data collected or derived under this cooperative agreement must be shared upon request with the Steering Committee, or its designee, for external monitoring pursuant to NIDA responsibilities under agreements with other government agencies (e.g. Food and Drug Administration) or commercial pharmaceutical companies where NIDA may co-develop investigational agents. At the conclusion of each protocol, the Lead Investigator will be required to direct the data coordinating center to produce a public use file of all related study data. The format and documentation of the data should be complete enough to replicate the studies outcomes and ensure its broader utilization by the drug abuse treatment community while maintaining subject confidentiality. c. Quality Assurance and Monitoring: All clinical trials are subject to quality control and monitoring as stated by CTN Quality Assurance (QA) and Monitoring policies and procedures. The Lead Investigator of each trial is primarily responsible for design of study QA monitoring plan according to the CTN policies and procedures. In addition, NIDA or its representative, the Clinical Coordinating Center, will provide periodic oversight and Quality Assurance monitoring of all clinical trial sites following the Good Clinical Practice (GCP) standards. Awardee agrees to permit on site monitoring for all of its community treatment provider sites. For medication trials, NIDA, when necessary, will be the holder of the Investigational New Drug application (IND). When there is an IND, NIDA will be primarily responsible for study control and monitoring as defined by FDA rules and regulations. When NIDA holds the IND, the RRTCs will be subject to review by NIDA to ensure adherence to GCP. The Awardee agrees to provide material and documentation needed to assure GCP compliance. d. Training: A Training Tracking System has been developed by the CTN to track the required training of staff throughout the network. The system tracks two components, staff training requirements and training attendance. The purpose of the system is to identify the training delivered and document that the training requirements have been satisfied. Reports are available to the CTN community via its secured web-based document repository (Livelink). Awardees agree to enter training information into this CTN wide system. e. Subject Safety/Oversight The RRTC will develop protocol-specific measures to assure the safety and protection of the rights of volunteers involved in the clinical studies, and other research projects, to be conducted under this cooperative agreement. The Principal Investigator assumes and accepts the primary responsibility for ensuring CTN studies are conducted in compliance with all federal regulations and NIDA policies and procedures. These include, but are not limited to, Title 21 CFR Parts 11, 50, 56, 312, and Title 45 CFR 46. The RRTC must be able to demonstrate that each institution and CTP has a current, approved, Institutional Assurance of Protection for Human Subjects on file with the Department of Health and Human Services Office for Human Research Protections; that each protocol and informed consent is approved by the recognized Institutional Review Board (IRB) prior to the enrollment of subjects in any study; and that each subject (or legal representative) has given necessary written informed consent prior to admission to any study conducted under this cooperative agreement. The Principal Investigator agrees and assures that adequate records will be maintained, and that access to these records will be available, to enable outside monitors to assess compliance with applicable federal laws and regulations. f. Unexpected Adverse Experience Reporting: The Principal Investigator of the RRTC agrees to implement and adhere to an adverse event tracking system operated by NIDA and adopted by the Steering Committee. g. Reporting Requirements: In addition to periodic financial and administrative reports required by NIH for administration of this cooperative agreement, the Awardee agrees to furnish the following reports according to the schedule indicated: CTN Node Operations Reports: Awardees are required and agree to provide quarterly reports of program activities to NIDA by the 10th day of the month following the end of programmatic quarters (90 days from the date of award). These reports include: 1) a quarterly progress report of the activities of the Node within the reporting period and 2) quarterly financial reports showing a breakdown of the costs incurred for both the RRTC and CTPs for the reporting period. The quarterly financial report shall include a total of all costs spent in previous quarters for that year as well as the current reporting period. This report is in addition to the yearly Federal Status Report (FSR) required by NIH. The CCTN/NIDA will define a recommended format and specify minimum content for these Program Operations Reports. CTN Research Project Reports: Awardees are required and agree to provide periodic reports of the research projects undertaken in the CTN. At minimum the Lead Investigator must provide timely information on the tasks, schedule, and costs associated with the development and implementation of a CTN research project. Enrollment information in a format and according to a schedule defined by NIDA and the Steering Committee are required for each CTN clinical research project. Other protocol-specific reports, such as those needed to monitor the safety and clinical effectiveness of drugs or other interventions under investigation will be required to allow the Steering Committee and Data and Safety Monitoring Board to monitor the research projects undertaken in the CTN. The Steering Committee will determine the nature, frequency, and content of reports as part of the protocol review and approval process Investigational New Drug (IND) Reports: Awardees are required and agree to provide reports according to regulations and guidelines established by the Food and Drug Administration (FDA). Data and other reports required of IND sponsors will be provided to the Steering Committee prior to dates established by the Steering Committee. Final Study Report: Lead Investigators are required to provide the Director, CCTN and the Steering Committee with a Final Study Report within 120 days of data lock upon completion of the protocol. The Final Study Report is a brief accounting of the history, participants, and milestones in the completion of the trial. The content and format are approved by the Steering Committee. h. Publication of Data: Prompt and timely presentation and publication in the scientific literature of findings resulting from research undertaken in the CTN is required. It is expected that the Lead Investigator will have an initial outcome paper completed and submitted to an appropriate peer-reviewed scientific journal within 180 days of data lock for the protocol. The Awardee agrees to acknowledge NIDA support in the publications and oral presentations resulting from research conducted under cooperative agreement. Prior to the submission of manuscripts for publication Awardees agree to provide preprint copies to the Steering Committee according to policies and procedures the Steering Committee may establish to monitor the presentation and publication of CTN results. i. Progress Review The CTN Steering Committee has established and will continue to elaborate procedures for monitoring the performance of the RRTCs and the CTPs participating in research under this cooperative agreement. Performance metrics, such as budget execution, subject enrollment, data acquisition and transmission, and study analysis and reports have been defined to permit NIDA and the CTN Steering Committee a means to assess progress of the Node and provide information needed to support future funding decisions. The inability of an RRTC to meet performance requirements and responsibilities defined in these Terms and Conditions, and further elaborated by the Steering Committee may result in an adjustment of funding, withholding of support, restriction of funds already awarded, or suspension or termination of the award. j. National Meetings: The Steering Committee may meet up to four (4) times each year. The Principal Investigator agrees to provide adequate support for participation in CTN meetings as required by the Steering Committee and its various operating sub- committees. The Principal Investigator agrees to support participation by CTP personnel as required by CTN projects. k. Conflict of Interest: Awardees are required to comply with 42 CRF part 50, subpart F “Responsibility of Applicants for promoting Objectivity in Research for Which PHS Funding is Sought.” In addition, the CTN Steering Committee has developed policies on Conflict of Interest and monitors compliance to that policy. The Conflict of Interest Policy addresses issues that may arise through financial ties between RRTC and CTP participants and the private sectors. Awardees will abide by the CTN Conflict of Interest Policy and ensure staff identified in the policy provide disclosure to the CCTN as required. This policy can be found at: http://grants.nih.gov/grants/policy/coi/index.htm or http://www.nida.nih.gov/CTN/policies.html l. Protocol Closure: Throughout the term of the cooperative agreement NIDA may request that a research project be terminated for reasons including: 1) insufficient subject accrual; 2) accrual goal for the protocol is met; 3) poor performance in conducting the protocol; 4) safety of the subjects in the study; 5) achievement of conclusive study results; and, 6) emergence of new information that diminishes the scientific importance of the study question. Financial support from NIDA through this cooperative agreement will cease upon project closure, except that funds may remain available for patients already enrolled in the study. 3. RRTC and CTPs: a. The RRTC agrees to negotiate and establish subcontracts with at least five community treatment programs (CTPs) to conduct research and training projects under this cooperative agreement. Each CTP must: -- Agree to participate in controlled clinical trials, including randomization methods for assignment of patients to experimental or control groups or randomization of therapists to different conditions; -- Screen and recruit adequate numbers of patients required to meet the expectation of specific protocols. This frequently requires recruiting one patient per week. -- Agree to provide routine clinical care to patients participating in protocols; -- Agree to provide experimental/standard care in accord with approved research protocols; -- Provide HIV risk reduction counseling and access to HIV testing; -- Provide HCV education and referral for testing and treatment; -- Maintain patient records and other source documents required for each protocol; --Collect clinical and laboratory data, including biological specimens when indicated; -- Cooperate with quality assurance activities of the CTN and adhere to guidelines set by the RRTC, the Steering Committee, and NIDA; -- Cooperate with NIDA’s Clinical Coordinating Center and Data and Statistics Center -- Participate in the development of research concepts and protocols for trials to be conducted in the CTN; -- Agree not to report data prior to collaborative reporting; -- Agree to periodic on-site audits by representatives of its RRTC, NIDA, or a NIDA designee to ensure appropriate use of investigational drugs; compliance with regulations for FDA, IRB approval or informed consent (compliance with 45 CFR 46); misconduct in science inquires; compliance with protocol specifications; quality assurance and accuracy of data recording; and completeness of reporting of adverse drug reactions. CTPs are not expected to participate in every CTN research project, but must adhere to the above terms when they choose to participate in a CTN research project. b. The RRTC shall establish agreements with CTPs that include, at minimum: 1) a statement of work defining the goals and objectives of the research projects to be undertaken under this cooperative agreement; 2) a budget for support of the research projects that clearly identifies the personnel, equipment, materials, and other costs required to successfully conduct high quality research in the community treatment program according to the requirements of specific protocols approved for implementation by the CTN Steering Committee; and 3) a financial and program reporting requirement, including access to data and materials, to facilitate CTN program operation and research project oversight and monitoring. 4. NIDA Staff Responsibilities NIDA staff do have and will have substantial scientific and programmatic involvement throughout the life of this cooperative agreement through technical assistance, and advice and coordination extending beyond normal program stewardship for grants, as described in these terms and conditions. The role of the NIDA staff as described throughout these Terms and Conditions is to assist and facilitate, but not to direct the research activities. Communication and interaction will occur primarily with the scientific leadership of the RRTC; however, NIDA may also interact directly with the Directors of any of the collaborating CTPs as needed. NIDA maintains a Logistic Support Center (LSC) through contract. These central resources support certain administrative coordinating functions of the CTN. These include: 1) Logistical support for meetings of the Network, e.g., CTN Steering Committee, subcommittees, workgroups and other Boards (the Advisory Board, the DSMB, etc.), 2) Reproduction and distribution of research and educational materials, including treatment protocols, training manuals, and instrumentation, 3) Development, reproduction, and distribution of materials publicizing the activities of the CTN. a. NIDA’s Scientific Role NIDA Collaborating Scientists (CSs) with expertise in behavioral therapies, medications development, and practice research may participate in the development of study plans and protocols, quality assurance and control activities, and in coordinating projects across scientific disciplines and CTN Nodes. NIDA CSs may initiate or participate in publications in accordance with established professional and NIH guidelines for authorship. The NIDA CSs will not, however, have a direct role in assessment, testing, or treatment of human subjects participating in studies under this cooperative agreement. A collaborating scientist is assigned such responsibility only with the approval of the Director, CCTN. The NIDA CCTN Director, and/or designated staff, will work closely with the CTN Steering Committee to assure that the research efforts are consistent with NIDA’s research objectives and complement other clinical trial activities supported by NIDA under other means. NIDA will serve as a resource, and will disseminate information regarding promising new therapies. NIDA staff will advise the clinical investigators, as requested or needed, of results from other trials (e.g., adverse experiences and study termination) that could influence the design, development, or conduct of clinical trials under this cooperative agreement. The following Boards will have approval authorities as indicated: NIDA Protocol Review Board: An expert board authorized by the NIDA Director that will review the final draft of the protocol submitted by the Lead Investigator and the Protocol Development Team for scientific and regulatory approval. Data and Safety Monitoring Board (DSMB). The DSMB is an independent expert board appointed by and reporting to the Director of NIDA that will review study plans and oversee and monitor the conduct of the clinical trials to ensure the safety of participants and the validity and integrity of the data. The DSMB will also make an independent assessment of the effectiveness of interventions under investigation and whether a trial will continue. One or more NIDA staff will serve as non-voting members on the DSMB. b. NIDA’s Role in Protocol Review and Approval In order for a CTN research project to be initiated, the study proposal must be mutually approved by the CTN Steering Committee and NIDA. Once notified that a clinical trial is under consideration, NIDA will evaluate the proposed trial according to NIDA’s treatment research agenda, its likelihood of timely completion; patient safety; compliance with Federal regulatory requirements; plans for interim monitoring and final analysis of results; and resource requirements. The Lead Investigator for the protocol is required to provide the CCTN with a cost projection and rationale for the resource requirements for protocol implementation. Prior to protocol approval as defined above, NIDA will provide no trial materials or permit expenditure of CTN funds to implement the research project unless and until the proposed protocol is approved. Disagreements arising during the protocol approval process may be submitted to an arbitration panel for resolution. A panel composed of one CTN designee, one NIDA designee, and a third member with drug abuse clinical trials expertise chosen by the other two members will be formed to review the NIDA decision and recommend an appropriate course of action to the Director, NIDA. These special arbitration procedures in no way affect the Awardee’s right to appeal an adverse determination in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. c. NIDA Approval to Enroll Study Participants CTN research projects may proceed upon the Lead Investigator receiving approval from the NIDA CCTN Director that enrollment may begin. The Lead Investigator is responsible for providing all necessary documentation of the readiness of each participating site to initiate participant enrollment. Such documentation will include 1) evidence of IRB approval for each clinical site, 2) evidence of data system readiness based on the successful test and certification by NIDA’s Data and Statistics Center, 3) evidence that all participating project personnel both at the CTP and the RRTC have received the training needed to conduct the research according to the protocol and that this information has been documented in the CTN Training Tracking Data Base and 4) evidence that the protocol quality assurance plans are in place to monitor the research project at participating clinical sites. d. NIDA’s Role During Protocol Conduct For ongoing research projects NIDA personnel and its contractors will monitor the safety of study participants through review of incremental case report form. For all clinical trials, NIDA will assign a Medical Officer who will be responsible for the review and disposition of adverse events that may arise in the course of a study. NIDA will prepare periodic reports profiling the conduct of the study including the safety of study participants for review by the CTN Data and Safety Monitoring Board (DSMB). e. NIDA’s Role in Protocol Closure The NIDA CCTN Director, and/or designated staff, will monitor the progress of CTN studies by reviewing data and other reports periodically submitted to NIDA. The independent NIDA Data and Safety Monitoring Board, consisting of experts from several disciplines, may determine a need to alter, suspend, or close an ongoing trial due to safety concerns or study performance issues. Additionally, NIDA may deem it necessary to deny access to further investigational drug supplies and deny the expenditure of additional NIDA funds (except where volunteers are already enrolled) if any of the following reasons apply: (1) scientific question no longer relevant, (2) slow accrual, (3) study will not answer questions intended in the proposed study plan, or (4) misuse of federal funds. Appeal of such a decision by the RRTC would proceed in the same manner as an appeal regarding the disapproval of a protocol prior to opening. f. NIDA Access to Data The NIDA CCTN Director, and/or designated staff, shall have access to all data generated under this cooperative agreement and may periodically review data recorded on clinical source documents, case report forms, or in electronic form. Data must be available for external checking against original source documents as required by NIDA, and Federal regulations pertaining to the responsibility of NIDA as an IND sponsor. The awardees will retain custody and primary rights to the data consistent with current HHS, PHS, and NIH policies, including a policy to provide public access to selected, significant data sets generated with the use of public funds, within a reasonable period of time after primary analysis and publication by the CTN. g. Clinical Trials Agreements It is expected that for some clinical trials proposed by the CTN Steering Committee, a pharmaceutical company collaborator will provide investigational agents for the trials. In order for the CTN, NIDA and the company to understand their respective responsibilities and rights, a Clinical Trials Agreement (CTA) will be negotiated and signed by NIDA and the company. Important terms of the agreement include IND sponsorship, safety and data monitoring, and access to trial data. Concurrence with the RRTC Principal Investigator will normally be obtained prior to execution of any final agreement that deviates significantly from the standard NIDA CTA. In general, terms in the CTA covering data access and sharing will conform to policies developed jointly by the CTN Steering Committee and NIDA. h. NIDA Review of CTN Compliance with Federally Mandated Regulatory Requirements The NIDA CCTN staff will review applicable regulatory requirements and advise CTN members of mechanisms to meet; (1) FDA regulations for studies involving investigational agents, and (2) the DHHS Office for Human Research Protections regulations for the protection of human volunteers in clinical research studies. i. Review of Performance The NIDA CCTN Director will review the performance of the CTN as a whole and of individual RRTCs. at least once every two years. Such reviews will include periodic reviews of the RRTC and its CTP sites for compliance with clinical and regulatory guidelines and success in achieving the performance standards established by the CTN Steering Committee. The review will be based on information provided in periodic progress reports defined elsewhere in these Terms and Conditions, and evaluations of site performance conducted by the CCTN staff. Insufficient patient accrual, substandard data quality, inadequate progress in executing the research agenda, or noncompliance with the Terms and Conditions of Award may result in a reduction in budget, withholding support, suspension, or termination of award. 5. Arbitration When agreement between an awardee and NIDA staff cannot be reached on scientific/programmatic issues that may arise after the award, an arbitration panel will be formed. A panel composed of one CTN designee, one NIDA designee, and a third member with drug abuse clinical trials expertise chosen by the other two members will be formed to review the NIDA decision and recommend an appropriate course of action to the Director, NIDA. These special arbitration procedures in no way affect the Awardee’s right to appeal an adverse determination in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. WHERE TO SEND INQUIRIES We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues: o Direct your questions about scientific/research issues to: Betty Tai, Ph.D. Center for the Clinical Trials Network National Institute on Drug Abuse, NIH, DHHS 6001 Executive Boulevard, Room 3103, MSC 9557 Bethesda, MD 20892-9557 Telephone: (301) 443-6697 FAX: (301) 443-2317 Email: btai@nida.nih.gov o Direct your questions about peer review issues to: Teresa Levitin, Ph.D. Office of Extramural Affairs National Institute on Drug Abuse, NIH, DHHS 6101 Executive Boulevard, Suite 234, MSC 8401 Bethesda, Maryland 20892-8401 Telephone: (301) 443-2755 FAX: (301) 443-0538 Email: tlevitin@mail.nih.gov o Direct your questions about financial or grants management matters to: Dr. Gary Fleming Chief, Grants Management Branch National Institute on Drug Abuse, NIH, DHHS 6101 Executive Boulevard, Room 270, MSC 8403 Bethesda, Maryland 20892-8403 Rockville, MD 20852 (for express/courier service) Telephone: 301-443-6710 Fax: 301-594-6849 E-mail: GF6S@NIH.GOV LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes the following information: o Descriptive title of the proposed research o Name, address, and telephone number of the Principal Investigator o Names of other key personnel o Participating institutions o Number and title of this RFA Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review. The letter of intent is to be sent by the date listed at the beginning of this document. The letter of intent should be sent to: DA05-001 Director Office of Extramural Affairs National Institute on Drug Abuse, NIH, DHHS 6101 Executive Boulevard, Suite 220, MSC 8401 Bethesda, Maryland 20892-8401 Telephone: (301) 443-2755 FAX: (301) 443-0538 Email: tlevitin@mail.nih.gov SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001). Applications must have a DUN and Bradstreet (D&B;) Data Universal Numbering System (DUNS) number as the Universal Identifier when applying for Federal grants or cooperative agreements. The DUNS number can be obtained by calling (866) 705-5711 or through the web site at http://www.dunandbradstreet.com/. The DUNS number should be entered on line 11 of the face page of the PHS 398 form. The PHS 398 document is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov. USING THE RFA LABEL: The RFA label available in the PHS 398 (rev. 5/2001) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf. SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Center for Scientific Review National Institutes of Health, DHHS 6701 Rockledge Drive, Room 1040, MSC 7710 Bethesda, MD 20892-7710 Bethesda, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to: DA05-001 Director Office of Extramural Affairs National Institute on Drug Abuse, NIH, DHHS 6101 Executive Boulevard, Suite 220, MSC 8401 Bethesda, Maryland 20892-8401 Telephone: (301) 443-2755 FAX: (301) 443-0538 Email: tlevitin@mail.nih.gov APPLICATION PROCESSING: Applications must be received on or before the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. Although there is no immediate acknowledgement of the receipt of an application, applicants are generally notified of the review and funding assignment within 8 weeks. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to an RFA, it is to be prepared as a NEW application. That is, the application for the RFA must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application. SUPPLEMENTARY INSTRUCTIONS Specific content must be present in the application to document the technical and scientific merit of the applicant's plan for a Node that will addresses the fundamental goals and collaborative nature of the CTN. The use of tables, diagrams, and organizational and flow charts is strongly encouraged. APPLICATION PACKAGE The application should conform to the general instructions and requirements of the PHS 398 (rev. 5/2001) with the exceptions noted below. Sections a-d need not be organized according to Specific Aims, Background and Significance, etc. as stated in the PHS 398 application kit. It is suggested that sections a-d be replaced with the following sections. Note, also the page limits described in a subsequent section of this announcement. SPECIFIC REQUIREMENTS FOR COMPETING CONTINUATION APPLICATIONS Progress Report Section An application from a currently funded Node will be a competing continuation. It is recognized that each competing continuation application will present both unique features and activities carried out in common with other CTN Nodes. Applications are expected to provide evidence of their contributions to shared CTN activities as well as to provide evidence of their unique strengths and accomplishments. A competing continuation application must include a progress report which at minimum consists of: 1. Evidence of efficient administrative structure/personnel in managing multi-site trials, ability to participate in multi-site trials; 2. A summary of research activities/accomplishments during the prior funding period, including a clear presentation of annual accrual to all participating protocols, and the gender/ethnic minority composition of recruited study populations, from affiliated CTPs and how well accrual met CTN accrual goals, and scientific publications and presentations; 3. Status of any concepts developed by the applicants, i.e., concepts developed and submitted by the Node and any concepts accepted for development CTN-wide; 4. Progress in developing and implementing research protocols, including the details of the process and organizational structure for protocol development and implementation, efficient and extensive Node training activities to ensure efficiency in performing protocols, QA to ensure adherence to protocol requirements and patient well being and safety, quality data management, etc.; 5. Evidence of ability to engage community treatment programs in bi- directional communications to bridge the research to practice gap; 6. Evidence of participation and leadership in CTN research and administrative activities; 7. Summary of unique contributions of the Node to CTN-wide activities in the prior funding period. REQUIREMENTS FOR ALL APPLICATIONS: The following sections are to be used by all applicants, both for new and competing continuation applications. 1. Understanding of and Ability to Contribute to the Mission of the CTN: This section should consist of a few pages to establish the applicant’s understanding of the CTN and describe how the proposed Node contributes to the CTN goals. 2. Administrative and Management Plans: The qualifications and experience of the Principal Investigator must be described. An individual should be designated as the coordinator for intra- Node research activities. His or her qualifications and experience should also be described. Each application must also demonstrate the ability to access professionals with the appropriate expertise to design and implement the proposed interventions and controlled clinical trials. Evidence of participation in multi-site clinical trials is desirable. It is important to demonstrate the Principal Investigator’s ability to contribute to the scientific agenda and commit a minimum of 50 percent of time to provide protocol mandated leadership for the clinical trial. The accrual of geographically diverse CTPs should be evident. Evidence of current or previous successful collaborations with community treatment programs and of participation in successful multi-site trials in collaboration with other research centers would be desirable. Plans for intra-Node communications encompassing all of the Node's CTPs should be specified. Diagrams and descriptions of proposed intra-Node committee structures should be given. Each applicant must demonstrate the ability to train and maintain the proficiency of RRTC and CTP personnel to successfully manage treatment and clinical trials research. 3. Research and Clinical Infrastructures: The plans should document the availability of appropriate expertise within the RRTC to design, implement, and analyze the results of proposed trials. The plans should describe the infrastructure for core functions, which include but are not limited to managing the participation of CTPs in CTN activities, staffing technical personnel for protocol design, development and implementation, and providing resources for and coordination of intra-Node activities. The plans should also elaborate on the infrastructure capabilities in research administration, project management, protocol design and development, quality assurance and regulatory affairs. The plans should describe the framework and procedures for training and supervision of treatment providers in the experimental and standard interventions that will be utilized in the CTN. Applicants must demonstrate access to diverse racial and ethnic populations through the aggregate of their proposed community treatment providers. 4. Collaborations between the RRTC and CTPs: The application should describe the relationships between the CTPs and RRTC. It should provide detailed descriptions of CTPs that will participate, with detailed descriptions of each CTP’s characteristics, including patient population characteristics, patient throughput, types of treatment currently delivered, and staff number, characteristics, and structure. See outline that follows this paragraph. Each CTP’s description is limited to two pages of text. It will be critical for the Node to recruit and retain sufficient CTPs to participate in multiple simultaneous trials. The possibility of expanding the number of CTPs should be addressed. The appendix should contain letters of agreement from CTP directors and tables, as needed, to describe the CTPs. For each Community Treatment Program (CTP) 1. Name of Organization 2. Address 3. Telephone 4. Fax Number 5. Director/Contact (person who will work with the CTN, serve on committees, etc.) 6. E-Mail Address of Director/Contact Characteristics of each CTP to include: 1. Number of clinical sites in organization 2. Static capacity -- at any one time, what is the CTP’s total patient census? 3. Annual patient admissions by treatment modality 4. Rural or urban -- is the CTP located in a rural or urban community? 5. Clinic patient characteristics: o Percent Black, African-American o Percent Hispanic, Latino o Percent White, Caucasian o Percent American Indian or Alaskan Native o Percent Asian or Pacific Islander 6. Gender breakdown of patients -- percent male, percent female 7. Age breakdown of patients -- percent adolescent (under 21), percent over 65 if known (Medicare) 8. Does this agency serve pregnant women, families with children, etc? Percent of clients who fall into these categories. 9. What kinds of HIV/HCV services are currently offered? 1) Education and prevention; 2) testing and counseling; and/or 3) treatment for HIV/HCV 10. Classify the CTP as either (“Drug-Free”) Psychosocial, Methadone (and Buprenorphine), or both 11. Does the CTP offer behavioral treatment? If so, what types of treatment are offered? Is treatment provided in individual or group sessions, or both? 12. Categorize setting as: 1) Outpatient; 2) Residential; 3) Post- residential; 4) IOP (Intensive Outpatient Treatment); 5) TC (Therapeutic Community) -- treatment beyond the standard 6-8 week program; 6) Day care -- all day 8-5, 5 days per week; or 7) Half-way House 13. Does the CTP treat patients who are classified as co-morbid? (Dually diagnosed) 14. Are faith-based treatment services part of the program? Please describe. 15. Primary source of program funding: Patient Fees, Public Insurance, Public grant or contracts, Private Insurance 16. Any other pertinent characteristics of the CTPs proposed in your grant An organizational chart to describe the functional structure of RRTC and CTP personnel in the design and implementation of a variety of clinical research projects should be provided in the body of the application (i.e., within the 45 pages). An organizational chart and a description of the RRTC operation should describe the relationship between the research and administrative functional units within the Node. Evidence of current or previous successful collaborations with the community treatment programs would be desirable. In each of these areas, it is crucial that the applicant describe how the treatment providers will function in true partnership with the RRTC in terms of research concept origination, protocol design, research project implementation, and administrative support services. Applicants should anticipate potential problems and challenges that may arise in this process and propose mechanisms for collaborative resolution among the Node participants. The NIH policy regarding consortium agreements must be considered in describing the relationship between the RRTC and the CTPs. 5. Research Concept: Applicants should not propose a detailed research protocol, but rather should provide a specific example of a research concept and an abbreviated plan that could be undertaken and is consistent with the RFA to take advantage of the unique capabilities of the CTN, including collaboration across Nodes. The concept should present a discussion of the types of research questions that could be addressed, research methods that might be used, and patient populations that might be employed. Particular emphasis should be placed on how the applicant proposes to ensure that the RRTC and the CTPs of the Node will work collaboratively at all levels, and that the Node will be able to work collaboratively with other Nodes and NIDA in multi-site clinical trials. It should be understood that the concept example may not necessarily be implemented in the CTN. The research plans for the proposed concept should include descriptions of research study design, interventions, outcome measures, and statistical considerations; access to appropriate patients; procedures for data management, a training plan, quality control and follow-up; procedures for monitoring and reporting adverse events; and information on human subjects’ protections. Finally, there should be a cost estimate displayed as a protocol budget. This concept must include details according to the SOPs detailed in the following web site. http://www.nida.nih.gov/CTN/policies.html 6. Human Subjects Research (research plan section e): The application should describe plans for human subject protections, data and safety monitoring as well as gender and minority information about patient populations for the CTN Node as a whole. 7. Other: There should be information on literature cited, contractual arrangements, etc. as specified in the PHS 398. Budget The budget and accompanying justification are not part of the 45 page limit. Applicants should include budget estimates and plans for participating in the CTN, organized around the areas of research planning, core functions, RRTC and CTP collaboration, and administrative and management plans. The applicant should prepare a separate detailed budget for 1) infrastructure to enable the RRTC to provide core functions for the Node (e.g., personnel, facilities, equipment, supplies, training costs, logistic support, travel, etc.); 2) CTP support to conduct clinical trials; 3) Lead Node responsibilities for the scientific leadership of research projects. As noted elsewhere in this RFA, funds for Node travel should be included to provide for participation in CTN related meetings. Page Limits To summarize the guidance above, the total length of the Research Plan, including the CTP descriptions and research concept and administrative and management plan should not exceed 45 pages. Descriptions of CTPs should not exceed 2 pages per program. Descriptions of research concept should not exceed 10 pages. Literature Cited and Consortium/Contractual Arrangements sections should be provided following the 45 pages and in total should not exceed 15 pages. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and responsiveness by NIDA. Incomplete and/or nonresponsive applications will not be reviewed. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIDA in accordance with the review criteria stated below. As part of the initial merit review, all applications will: o Undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed and assigned a priority score o Receive a written critique o Receive a second level review by the National Advisory Council on Drug Abuse. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to evaluate the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. The scientific review group will address and consider each of the following criteria in assigning the application’s overall score, weighting them as appropriate for each application. o Significance o Approach o Innovation o Investigator o Environment The application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. 1. UNDERSTANDING THE CTN o How well does the proposed Node (i.e., the applicant RRTC and its affiliated community treatment programs) demonstrate an understanding of the scientific agenda of the Clinical Trials Network (CTN)? o To what extent would the proposed Node likely contribute or continue to contribute to the goals and enhance the capability of a nationwide CTN? 2. ADMINISTRATIVE AND MANAGEMENT PLANS o How strong are the plans for overall Node management and operations, including the structure and mechanisms for effective intra-Node communication and collaboration and involving appropriate personnel in the design and implementation of protocols? o How strong are the applicant's previous experience and plans for training RRTC and community treatment personnel, including therapists and research associates, in implementing multi-site clinical trials? o How strong are the plans for effective interaction and coordination with other Nodes and NIDA? 3. RESEARCH AND CLINICAL INFRASTRUCTURE o Is there sufficient evidence that the proposed Principal Investigator (PI) will be (or has devoted) adequate time to carry out the work of the CTN? (Must be a minimum of 50%) o How strong are the previous research experience and other qualifications of the PI and other key staff in design, administration, and management of multi-site clinical trials, including quality control, quality assurance, and data management procedures? o How strong are the qualifications of key personnel and scientific staff in the areas of the proposed research concept and in the more general skills needed to develop, conduct, and analyze clinical trials? o How good are the available resources and proposed personnel for administering Node participation in clinical trials, including adequacy of procedures to collect, monitor, and analyze the data and assure the safety of patients/participants? o How strong is the evidence of infrastructure capabilities in project management, protocol development, and knowledge of regulatory affairs? o How strong is the Node’s capacity to include appropriate representation of gender, minorities and their subgroups, and subjects with a range of ages appropriate for the scientific goals of the research? o How strong is the Node’s capacity to conduct research on HIV/AIDS and substance abuse? 4. COLLABORATION BETWEEN RRTC AND CTPs o Is there a record of previous RRTC-CTP collaboration, including orienting community personnel to protocol requirements, organizing scientific and educational meetings for those participating in the clinical trials, and participating in inter-group clinical trials.? o What is the quality of plans for involving CTPs in the research and organizational activities of the CTN? o How well developed are the RRTC's criteria for selecting CTPs with diverse geographic and population representation (as balanced by constraints of reasonable management)? o How good are the quality of the proposed CTPs and the experience of their program directors? o To what extent do the proposed CTPs vary programmatically? To what extent are they able to accrue a demographically diverse patient population? o How feasible are CTP plans for patient enrollment and retention? How well do the CTPs demonstrate their ability to accrue patients at an adequate rate to support multi-site clinical trials? 5. RESEARCH PLANS o How well does the proposed research concept demonstrate knowledge of state- of-the-art research designs, methodologies, and operations? o Does the plan have the potential to produce a major improvement in the quality and effectiveness of drug treatment? 6. PROGRESS (For competing continuation applications): Evaluate the adequacy of progress in: o developing and implementing protocols o subject accrual and retention o data management o evaluation/monitoring of Node activities o publication/presentation of research findings, and other dissemination of findings o level of participation and leadership in CTN-wide protocols o level of participation and leadership in CTN-wide committees o assess unique strengths and limitations this node brings to the CTN as a whole 7. OTHER In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The adequacy of plans to include both genders, minorities and their subgroups, and children as appropriate for the scientific goals of the research. o Plans for the recruitment and retention of subjects will also be evaluated. o The adequacy of the proposed protection for humans, animals or the environment, to the extent they may be adversely affected by the project proposed in the application. o The plans for data and safety monitoring will be assessed. 8. BUDGET o The reasonableness of the proposed budget and duration in relation to the proposed research. o How appropriate are the budget estimates for infrastructure to enable the RRTC to provide core functions for the Node (e.g., personnel, facilities, equipment, supplies, logistic support, travel)? o How appropriate are budget estimates for CTP support to conduct the clinical trials? o How adequate are plans for budgetary control and oversight? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the following items will be considered in the determination of scientific merit and the priority score: PROTECTION OF HUMAN SUBJECTS FROM RESEARCH RISK: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. (See criteria included in the section on Federal Citations, below). INCLUSION OF WOMEN, MINORITIES AND CHILDREN IN RESEARCH: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See Inclusion Criteria in the sections on Federal Citations, below). CARE AND USE OF VERTEBRATE ANIMALS IN RESEARCH: If vertebrate animals are to be used in the project, the five items described under Section f of the PHS 398 research grant application instructions (rev. 5/2001) will be assessed. ADDITIONAL REVIEW CONSIDERATIONS Sharing Research Data: Applicants requesting more than $500,000 in direct costs in any year of the proposed research must include a data sharing plan in their application. The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or priority score. BUDGET: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Date: September 14, 2004 Application Receipt Date: October 14, 2004 Peer Review Date: December 2004-January 2005 Council Review: May 2005 Earliest Anticipated Start Date: July 2005 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific merit (as determined by peer review) o Availability of funds o Programmatic priorities, including program balance, ability to use the CTN as a platform for training clinical researchers and as a platform for other research (e.g., health services, genetics, and HIV/AIDS), and geographic representation. REQUIRED FEDERAL CITATIONS ANIMAL WELFARE PROTECTION: Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf), as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm), as applicable. HUMAN SUBJECTS PROTECTION: Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained. http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm DATA AND SAFETY MONITORING PLAN: Data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose- finding studies (phase I); efficacy studies (phase II); efficacy, effectiveness and comparative trials (phase III). The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risk to the participants. (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, June 12, 1998: http://grants.nih.gov/grants/guide/notice-files/not98-084.html). SHARING RESEARCH DATA: Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible. http://grants.nih.gov/grants/policy/data_sharing Investigators should seek guidance from their institutions, on issues related to institutional policies, local IRB rules, as well as local, state and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score. INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at http://grants.nih.gov/grants/funding/children/children.htm REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (see http://escr.nih.gov). It is the responsibility of the applicant to provide, in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s)to be used in the proposed research. Applications that do not provide this information will be returned without review. HIV/AIDS COUNSELING AND TESTING POLICY FOR THE NATIONAL INSTITUTE ON DRUG ABUSE: Researchers funded by NIDA who are conducting research in community outreach settings, clinical, hospital settings, or clinical laboratories and have ongoing contact with clients at risk for HIV infection, are strongly encouraged to provide HIV risk reduction education and counseling. HIV counseling should include offering HIV testing available on-site or by referral to other HIV testing service for persons at risk for HIV infection including injecting drug users, crack cocaine users, and sexually active drug users and their sexual partners. For more information see http://grants.nih.gov/grants/guide/notice-files/NOT-DA-01-001.html. NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS: The National Advisory Council on Drug Abuse recognizes the importance of research involving the administration of drugs to human subjects and has developed guidelines relevant to such research. Potential applicants are encouraged to obtain and review these recommendations of Council before submitting an application that will administer compounds to human subjects. The guidelines are available on NIDA's Home Page at http://www.nida.nih.gov under the Funding, or may be obtained by calling (301) 443-2755. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this PA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. STANDARDS FOR PRIVACY OF INDIVIDUALLY IDENTIFIABLE HEALTH INFORMATION: The Department of Health and Human Services (DHHS) issued final modification to the “Standards for Privacy of Individually Identifiable Health Information”, the “Privacy Rule,” on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR). Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on “Am I a covered entity?” Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html. URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.healthypeople.gov/. AUTHORITY AND REGULATIONS: This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92). All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.
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